rs5952647

Positions:

• chrX-44875364-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291415.2(KDM6A):​c.225+1377A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 110,949 control chromosomes in the GnomAD database, including 7,661 homozygotes. There are 11,285 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (7661 hom., 11285 hem., cov: 23)
• Consequence: KDM6A NM_001291415.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542

Genes affected

KDM6A (HGNC:12637): (lysine demethylase 6A) This gene is located on the X chromosome and is the corresponding locus to a Y-linked gene which encodes a tetratricopeptide repeat (TPR) protein. The encoded protein of this gene contains a JmjC-domain and catalyzes the demethylation of tri/dimethylated histone H3. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM6A	NM_001291415.2	c.225+1377A>G		intron_variant		ENST00000611820.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM6A	ENST00000611820.5	c.225+1377A>G		intron_variant		1	NM_001291415.2	P4

Frequencies

GnomAD3 genomes AF: 0.354 AC: 39268 AN: 110897 Hom.: 7648 Cov.: 23 AF XY: 0.339 AC XY: 11240 AN XY: 33121

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.0733

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.251

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.354 AC: 39329 AN: 110949 Hom.: 7661 Cov.: 23 AF XY: 0.340 AC XY: 11285 AN XY: 33183

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.318

Alfa AF: 0.209 Hom.: 13670

Bravo AF: 0.371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5952647; hg19: chrX-44734610;